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- Title
Valganciclovir modulates the tumor necrosis factor axis molecules expression and CD4+ T-cell subsets in disseminated Kaposi Sarcoma patients.
- Authors
Ramon-Luing, Lucero A; Flores-Gonzalez, Julio; Angel García-Rojas, Luis; Islas-Muñoz, Beda; Volkow-Fernández, Patricia; Chavez-Galan, Leslie
- Abstract
Valganciclovir (VGC) was used in a randomized clinical trial in patients with disseminated Kaposi Sarcoma/human immunodeficiency virus (DKS/HIV) as add-on therapy to evaluate the proinflammatory axis tumor necrosis factor (TNF) and its receptors (TNFRs) in T cells. Two treatment schedules were used: an experimental regime (ER) and a conventional treatment (CT). Mononuclear cells from patients with DKS/HIV were obtained at baseline (W0), 4 (W4), and 12 weeks (W12). Ten DKS/HIV patients received CT (antiretroviral therapy [cART]) and 10 ER (valganciclovir [VGC] initially, plus cART at the fourth week). HIV+ without KS and HIV− patient groups were included as controls. Correlation between T-cell subsets and HHV-8 viral load (VL) and a multivariate linear regression was performed. Data showed that DKS/HIV patients have an increased frequency of CD8+ T cells, which display a high density of CD8 expression. The ER scheme increases naïve and central memory CD4+ T cells at W4 and W12 of follow-up and induces a balanced distribution of activated CD4+ T-cell subsets. Moreover, ER decreases solTNFR2 since W4 and CT decreased the transmembrane forms of TNF axis molecules. Although CT induces a positive correlation between HHV-8 VL and TNFRs, the use of ER positively correlates with TNF and TNFRs levels through follow-up and a moderate correlation with HHV-8 VL and TNF soluble levels. In conclusion, VGC, as an add-on therapy in DKS/HIV patients, gradually modulates the activation of CD4+ T-cell subsets and the TNF/TNFRs axis, suggesting a better regulation of the inflammatory status. Experimental regiment includes 4 weeks of valganciclovir before starting the antiretroviral therapy in DKS/HIV patients. Experimental regime (ER) induces a homogeneous distribution of activated CD4+ T cells and modulates efficiently the tumor necrosis factor (TNF) receptors (TNFR1 and TNFR2) levels. ER can provide a clinical benefit because an exacerbated inflammatory process could be avoided. Graphical Abstract
- Subjects
TUMOR necrosis factors; KAPOSI'S sarcoma; VALGANCICLOVIR; CD4 antigen; T cells
- Publication
Clinical & Experimental Immunology, 2024, Vol 215, Issue 2, p190
- ISSN
0009-9104
- Publication type
Article
- DOI
10.1093/cei/uxad115